Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature sensitive phenotype

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Item Type:	Article
Title:	Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature sensitive phenotype
Creators Name:	Oji, V., Hautier, J.M., Ahvazi, B., Hausser, I., Aufenvenne, K., Walker, T., Seller, N., Steijlen, P.M., Kuester, W., Hovnanian, A., Hennies, H.C. and Traupe, H.
Abstract:	Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. Here we report on a series of ten BSI patients. Our genetic, ultrastructural and biochemical investigations show that BSI is caused by transglutaminase-1 (TGase-1) deficiency. Altogether we identified 13 mutations in TGM1 - among them seven novel missense mutations and one novel nonsense mutation. Structural modelling for the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to solvent in a cavity of the enzyme. Cryosections of healthy skin areas demonstrated an almost normal TGase activity, in contrast to the affected BSI skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The distribution of TGase-1 substrates in the epidermis of affected skin corresponded to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3 and cathepsin D was reduced. Digital thermography validated a striking correlation between warmer body areas and presence of scaling in patients suggesting a decisive influence of the skin temperature. In situ TGase testing in skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25 degrees C to 37 degrees C. We conclude that BSI is caused by TGase-1 deficiency and suggest that it is a temperature sensitive phenotype.
Keywords:	Chromosome Mapping, DNA Sequence Analysis, Ichthyosis, Skin, Missense Mutation, Molecular Models, Nonsense Codon, Phenotype, Temperature, Transglutaminases
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	15
Number:	21
Page Range:	3083-3097
Date:	1 November 2006
Official Publication:	https://doi.org/10.1093/hmg/ddl249
PubMed:	View item in PubMed

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